Preventing transmission of schistosomiasis by controlling the snail (B. glabrata) population is one approach to combating this disease. The use of resistant snails to replace susceptible ones (a genetic control method) is an approach that has not been thoroughly explored. Genetics play a very crucial role in compatibility. B. glabrata compatibility to the invading schistosome differs considerably between susceptible and resistant stocks as well as within the same stock that have undergone self-fertilization. One aim of this study is to examine a strain of B. glabrata that has been obtained through selection and self-fertilization from F1 through F9 generations and beyond and compare their morphology and genetics in relation to their susceptibility observed phenotype. A histological comparison will be made between these snails by using light and electron microscopy on the amoebocyte producing organ, the albumen gland, the ovotestis, and the host/parasite response to the parasite at different time periods following infection. The second aim is to undertake a molecular approach to test the hypothesis that genotypic differences are responsible for the specific phenotypic variations seen among snails with different schistosome susceptibilities. Specifically, brain and albumen gland protein profiles will be compared and antibodies made against those that show variability. This will determine if differences in the protein patterns correlate with the snails' ability to sustain S. mansoni infection. A cDNA library will be constructed for the specific organ (e.g. albumin gland) showing gross morphological and molecular differences associated with the non-susceptible phenotype; however, a brain cDNA library is available to us. Gene(s) encoding proteins involved in this phenotype will be identified by subtractive hybridization and antibody screening. The broad objective is to provide additional information on the specific mechanisms involved in the genetic regulation of host-parasite susceptibility that will assist in determining if the genetic control method is a viable option for controlling schistosomiasis.